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AIMS: Access to joint replacement is being restricted for patients with comorbidities in a number of high-income countries. However, there is little evidence on the impact of comorbidities on outcomes. The purpose of this study was to determine the safety and effectiveness of hip and knee arthroplasty in patients with and without comorbidities. METHODS: In total, 312,079 hip arthroplasty and 328,753 knee arthroplasty patients were included. A total of 11 common comorbidities were identified in administrative hospital records. Safety risks were measured by assessing length of hospital stay (LOS) and 30-day emergency readmissions and mortality. Effectiveness outcomes were changes in Oxford Hip or Knee Scores (OHS/OKS) (scale from 0 (worst) to 48 (best)) and in health-related quality of life (EQ-5D) (scale from 0 (death) to 1 (full health)) from immediately before, to six months after, surgery. Regression analysis was used to estimate adjusted mean differences (LOS, change in OHS/OKS/EQ-5D) and risk differences (readmissions and mortality). RESULTS: Patients with comorbidities had a longer LOS and higher readmission and mortality rates than patients without. In hip arthroplasty patients with heart disease, for example, LOS was 1.20 days (95% confidence interval (CI) 1.15 to 1.25) longer and readmission rate was 1.52% (95% CI 1.34% to 1.71%) and mortality 0.19% (95% CI 0.15% to 0.23%) higher. Similar patterns were observed for knee arthroplasty patients. Patients without comorbidities reported large improvements in function (mean improvement OHS 21.3 (SD 9.91) and OKS 15.9 (SD 10.0)). Patients with comorbidities reported only slightly smaller improvements. In patients with heart disease, mean improvement in OHS was 0.39 (95% CI 0.27 to 0.51) and in OKS 0.56 (95% CI 0.45 to 0.67) less than in patients without comorbidities. There were no significant differences in EQ-5D improvement. CONCLUSION: Comorbidities were associated with small increases in adverse safety risks but they have little impact on pain or function in patients undergoing hip or knee arthroplasty. These results do not support restricting access to hip and knee arthroplasty for patients with common comorbidities. Cite this article: Bone Joint J 2021;103-B(1):56-64.

OBJECTIVES: Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis.METHODS: Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients).RESULTS: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood CONCLUSION: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.

Objectives: Imaging of joint inflammation provides a standard against which to derive an updated disease activity score (DAS) for rheumatoid arthritis (RA). Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with ultrasound-assessed synovitis.Methods: Early RA patients from two observational cohorts (n=434 & n=117), and a clinical trial (n=59) were assessed at intervals up to 104 weeks from baseline; all ultrasound scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined ultrasound grey scale and power Doppler scores (GSPD) with TJC28 & SJC28, CRP, ESR, general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability; coefficients learned from training data defined a re-weighted DAS28 which was validated against radiographic progression in independent data (3037 observations; 717 patients).Results: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A 2-component model including SJC28 and CRP outperformed a 4-component model (R-squared 0.235, 0.392, 0.380 vs. 0.232, 0.380, 0.375 respectively). The re-weighted 2-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihoodConclusion: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.

Objective To compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart. Methods Patients with IP were recruited to the Norfolk Arthritis Register from 1990 to 1994 (cohort 1 (C1)) and from 2000 to 2004 (cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (Health Assessment Questionnaire (HAQ)) were compared between the cohorts using population-average negative binomial regression and generalised estimating equation analysis, respectively. Risk of 10-year mortality was compared between cohorts using Cox models. Risk of cardiovascular disease (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression. Results In total 1653 patients were recruited (C1=1022, C2=631). Patients in C2 had 17% lower SJC51 than C1 over 10 years (95% CI −23% to −10%), whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared with C1 (all-cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: subhazard ratio 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all-cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24). Conclusion Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.

Objective: To compare the 10 year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart.Methods: Patients with IP were recruited to the Norfolk Arthritis Register from 1990-94 (Cohort 1 (C1)) and 2000-04 (Cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (HAQ) were compared between the cohorts using population average negative binomial regression and generalised estimating equation analysis respectively. Risk of 10 year mortality was compared between cohorts using Cox models. Risk of cardiovascular (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression.Results: In total 1653 patients were recruited (C1 = 1022, C2 = 631). Patients in C2 had 17% lower SJC51 than C1 over ten years (95% CI -23% to -10%) whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared to C1 (all cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: SHR 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24).Conclusion: Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.

Objective To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease‐modifying antirheumatic drugs/steroids) and mortality and disability during follow‐up. Methods Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1–3, 5, 7, 10, 15, and 20. Disease activity (swollen joint count [SJC]/tender joint count [TJC]), disability (Health Assessment Questionnaire disability index [HAQ DI]), and mortality over 20 years were determined. Associations between treatment group (early treatment [ET], treatment ≤6 months after symptom onset; late treatment [LT], treatment >6 months after symptom onset; never treatment [NT], no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed‐effects linear regression, respectively. Inverse weights were used to account for confounding by indication and censoring. Results This study included 602 patients with RA (median age 56 years [interquartile range 44–68 years]; 65.9% women). The median SJCs and TJCs were low during the follow‐up period (1–3 swollen joints and 3–6 tender joints). The median HAQ DI score increased after year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk of mortality was reduced in the ET and LT groups compared with that in the NT group. The ET group and the NT group had comparable HAQ DI scores during the follow‐up period (β = 0.03, 95% confidence interval [95% CI] −0.06, 0.12), while the HAQ DI score was increased in the LT group (for LT versus NT, β = 0.10 [95% CI 0.02, 0.17]). Conclusion The results of this study indicate the importance of early treatment with regard to the long‐term outcomes in patients with RA.

Objective To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and disability during follow-up. Methods Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1–3, 5, 7, 10, 15, and 20. Disease activity (swollen joint count [SJC]/tender joint count [TJC]), disability (Health Assessment Questionnaire disability index [HAQ DI]), and mortality over 20 years were determined. Associations between treatment group (early treatment [ET], treatment ≤6 months after symptom onset; late treatment [LT], treatment >6 months after symptom onset; never treatment [NT], no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed-effects linear regression, respectively. Inverse weights were used to account for confounding by indication and censoring. Results This study included 602 patients with RA (median age 56 years [interquartile range 44–68 years]; 65.9% women). The median SJCs and TJCs were low during the follow-up period (1–3 swollen joints and 3–6 tender joints). The median HAQ DI score increased after year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk of mortality was reduced in the ET and LT groups compared with that in the NT group. The ET group and the NT group had comparable HAQ DI scores during the follow-up period (β = 0.03, 95% confidence interval [95% CI] −0.06, 0.12), while the HAQ DI score was increased in the LT group (for LT versus NT, β = 0.10 [95% CI 0.02, 0.17]). Conclusion The results of this study indicate the importance of early treatment with regard to the long-term outcomes in patients with RA.

Objectives. To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years.Methods. Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression.Results. Of 589 RA patients [median age 56 years (IQR 45–68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient’s risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [β = 0.17 (95% CI 0.03, 0.32)].Conclusion. HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment.

Objective: Rheumatoid arthritis (RA) susceptibility HLA–DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes. Methods: We tested the association of RA susceptibility HLA–DRB1 amino acids with the C-reactive protein (CRP) level, the tender joint count (TJC), the swollen joint count (SJC), the Disease Activity Score in 28 joints (DAS28), and the Health Assessment Questionnaire (HAQ) score in the Norfolk Arthritis Register (NOAR) and Early Rheumatoid Arthritis Study (ERAS) cohorts. Longitudinal modeling of disease activity/outcomes was performed using generalized linear latent and mixed models. Mediation analysis was performed using directed acyclic graphs to investigate the paths from genetic factors to outcome. Results: A total of 2,158 patients were available for analysis in the NOAR cohort. Valine at position 11 showed the strongest association with the CRP level (P = 2.21 × 10−6), the SJC (P = 7.51 × 10−6), and the DAS28 (P = 0.002); it was marginally associated with the HAQ score (P = 0.044) but not with the TJC. The same amino acid and haplotype risk hierarchy observed for susceptibility and radiographic severity was observed for the CRP level and nonradiographic measures of disease activity/outcome, apart from the TJC. The results were replicated in the ERAS cohort. The effect of valine at position 11 on the SJC was mainly mediated by anti–citrullinated protein antibody status, the effect of which was mainly mediated by inflammation; however, the effect of valine at position 11 was also independent of the CRP level (P = 1.6 × 10−4). Conclusion: Genetic markers of RA susceptibility located within HLA–DRB1 determine the levels of clinical and systemic inflammation independently, and also determine all objective measures of disease activity and outcome.